Characterization of Hippocampal Neural Activity in Evidence Accumulation and Decision-Making Project Summary/Abstract In an ever-changing environment, the ability to accumulate and evaluate evidence is crucial for optimal decision-making. The hippocampus is thought to embody a cognitive map and has been well-studied in navigation and foraging tasks. However, it is unknown how the hippocampus behaves when evidence for decision-making must be accumulated over time. We will use calcium imaging to measure neural activity from hundreds of CA1 neurons simultaneously in mice navigating a virtual T-maze with noisy visual cues that inform the animal of the correct decision (left or right turn) at the end of the maze. Our first aim will be to build a comprehensive model of CA1 neural activity during this task that can account for the primary variables of evidence and place, possibly multiplexed with other perceptual and behavioral variables. Promising preliminary evidence suggests that CA1 neurons encode spatial information that is modulated by the amount of evidence that has been received. In addition to single cell activity, evidence also suggests that CA1 neurons can organize into multiple sequences in the same environment. Our second aim is to evaluate whether the sequential nature of CA1 population activity holds task-relevant information beyond individual neuron activity. Our third aim is to investigate the biophysical underpinnings of these sequences and whether their formation takes place as a causal result of population activity in the CA1. To achieve these goals, we will utilize rodent virtual reality behavior, multidimensional analysis tools to investigate the coordinated activity of large populations of neurons, in addition to combining cellular-resolution optogenetic activation/inhibition simultaneously with 2-photon calcium imaging. Together, these experiments will establish a role for the hippocampus in a previously unstudied context. Beyond the significance for basic science research, understanding the neural processes behind evidence accumulation and decision-making also has important implications in the management of psychiatric and neurological disorders, such as obsessive-compulsive disorder, addiction, or attention deficit hyperactivity disorder, in which these functions are disrupted.